Equine glucagon-like peptide-1 receptor physiology
Background Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in ani...
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PeerJ Inc.
2018-01-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/4316.pdf |
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| author | Murad H. Kheder Simon R. Bailey Kevin J. Dudley Martin N. Sillence Melody A. de Laat |
| author_facet | Murad H. Kheder Simon R. Bailey Kevin J. Dudley Martin N. Sillence Melody A. de Laat |
| author_sort | Murad H. Kheder |
| collection | DOAJ |
| description | Background Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated. Methods Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified in vitro. Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism in vitro, using concentration-response experiments. Results The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced (P = 0.08) insulin secretion by 27%. Discussion The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation. |
| first_indexed | 2024-03-09T07:02:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:02:58Z |
| publishDate | 2018-01-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
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| spelling | doaj.art-2deaa023ee9d40c8b99c7d8ad5bf2efa2023-12-03T09:46:24ZengPeerJ Inc.PeerJ2167-83592018-01-016e431610.7717/peerj.4316Equine glucagon-like peptide-1 receptor physiologyMurad H. Kheder0Simon R. Bailey1Kevin J. Dudley2Martin N. Sillence3Melody A. de Laat4Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, AustraliaFaculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, AustraliaInstitute for Future Environments, Queensland University of Technology, Brisbane, Queensland, AustraliaScience and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, AustraliaScience and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, AustraliaBackground Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated. Methods Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified in vitro. Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism in vitro, using concentration-response experiments. Results The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced (P = 0.08) insulin secretion by 27%. Discussion The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation.https://peerj.com/articles/4316.pdfEquine metabolic syndromeGLP-1 receptorHorseInsulinIncretinLaminitis |
| spellingShingle | Murad H. Kheder Simon R. Bailey Kevin J. Dudley Martin N. Sillence Melody A. de Laat Equine glucagon-like peptide-1 receptor physiology PeerJ Equine metabolic syndrome GLP-1 receptor Horse Insulin Incretin Laminitis |
| title | Equine glucagon-like peptide-1 receptor physiology |
| title_full | Equine glucagon-like peptide-1 receptor physiology |
| title_fullStr | Equine glucagon-like peptide-1 receptor physiology |
| title_full_unstemmed | Equine glucagon-like peptide-1 receptor physiology |
| title_short | Equine glucagon-like peptide-1 receptor physiology |
| title_sort | equine glucagon like peptide 1 receptor physiology |
| topic | Equine metabolic syndrome GLP-1 receptor Horse Insulin Incretin Laminitis |
| url | https://peerj.com/articles/4316.pdf |
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